POS0066 THE PHENOTYPE OF MIXED CONNECTIVE TISSUE DISEASE PATIENTS HAVING ASSOCIATED INTERSTITIAL LUNG DISEASE
Authors: G. Boleto, S. Reiseter, A. M. Hoffmann-Vold, A. Mirouse, P. Cacoub, M. Matucci-Cerinic, M. Silvério-António, J. E. Fonseca, V. Riccieri, E. Le Tallec, A. Lescoat, J. L. Tandaipan, I. Castellví, P. Airò, M. Kuwana, H. Kavosi, J. Avouac, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2022)

Background Mixed connective tissue disease (MCTD) is a rare autoimmune condition characterized by Raynaud’s phenomenon, positivity of autoantibodies targeting the U1 small nuclear ribonucleoprotein particle (U1RNP), and various clinical features of other connective tissue diseases (1-2). Interstitial lung disease (ILD) is an established complication of the disease that is suspected to affect morbidity and mortality (3). However, little is known about MCTD-associated ILD (MTCD-ILD) phenotype including first presentation, outcomes and predictive factors for progression. Objectives To compare two distinct populations of MCTD patients with and without associated ILD and to identify predictive factors for lung progression and severity. Methods International multicenter retrospective study (12 tertiary hospitals). To be included, patients were required to fulfill at least one MCTD international classification criteria (4). ILD was defined by the presence of typical chest high-resolution computed tomography (HRCT) abnormalities. Patients were divided into two groups: with or without ILD, at a ratio of 1:1 and matching on disease duration (+/- 2 years). Results 300 patients were included. Mean age at MCTD diagnosis was 39.7±15.4 years and 191 (63.7%) were women. At baseline, we identified several variables associated with the presence of ILD: older age (42.2 vs 37.5 years, p=0.01), scleroderma-like phenotype (38.7 vs 27.3%, p=0.03), upper gastro-intestinal (GI) symptoms (54.7 vs 30.7%, p&lt;0.001), forced vital capacity (FVC) &lt;80% (80.4 vs 95.3%, p&lt;0.0001), diffusing capacity for carbon monoxide (DLCO) &lt;80% (62.4 vs 74.8%, p&lt;0.0001), anti-topoisomerase antibodies (6 vs 0 patients, p=0.01), SSA/Ro antibodies positivity (29.3 vs 19.3%, p=0.02), cryoglobulinemia (5.3 vs 1.3%, p=0.04) and elevated C-reactive protein (CRP) &gt;5mg/L (54.7 vs 28.7%, p&lt;0.001). Among the previous variables older age (OR 1.03, 95% CI 1.01 to 1.05), upper GI symptoms (OR 1.92, 95% CI 1.03 to 3.58) and CRP &gt;5mg/L (OR 8.77, 95% CI 2.94 to 26.22) remained significantly associated with the presence of ILD by multivariate analysis. Patients with MTCD-ILD were more likely to be treated with synthetic immunosuppressant agents (68.7 vs 49.3%, p&lt;0.001) including mycophenolate mofetil (MMF) (7.3 vs 1.3%, p=0.03). Mean follow-up was 7.8±5.5 years. In longitudinal analyses, mortality was higher in the MTCD-ILD group (8 vs 0 deaths, p&lt;0.001). In the MCTD-ILD group, among 60 patients with complete data on lung function tests, we observed a FVC decline &gt;10% in 33 (55%) patients. With regards to the risk of progression, we identified that history of digital ulcers (DU) was a risk factor for FVC decline &gt;10% (OR 6.75, 95% CI 1.7-26.4, p=0.006). Conclusion In this large international cohort of patients with MTCD, we identified several factors associated with ILD development. Our findings highlight a high risk of mortality in MCTD-ILD patients and that digital ulceration seems to be at risk of more progressive ILD. References [1]Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR. Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. févr 1972;52(2):148‑59. [2]Gunnarsson R, Hetlevik SO, Lilleby V, Molberg Ø. Mixed connective tissue disease. Best Pract Res Clin Rheumatol. févr 2016;30(1):95‑111. [3]Gunnarsson R, Aaløkken TM, Molberg Ø, Lund MB, Mynarek GK, Lexberg AS, et al. Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study. Ann Rheum Dis. déc 2012;71(12):1966‑72. [4]Cappelli S, Bellando Randone S, Martinović D, Tamas M-M, Pasalić K, Allanore Y, et al. « To be or not to be, » ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum. févr 2012;41(4):589‑98. Disclosure of Interests None declared